LAUSR

A 52-year-old woman presented with a several-year history of progressive pruritic pigmented skin lesions with urticarial reactions to scratching and intermittent gastrointestinal distress. Physical examination was unremarkable aside from her skin lesions, and her serum tryptase was not elevated. A skin biopsy demonstrated cutaneous mastocytosis (Fig. 1, panel A) and she was referred for bone marrow examination to exclude systemic mastocytosis. Mast cells, while focally slightly increased in number in her bone marrow, formed no significant aggregates (Fig. 1, panel B). Occasional mast cells were shown immunohistochemically to aberrantly express CD2 (Fig. 1, panel C) or CD25 (Fig. 1, panel D), and aspirate specimens revealed abnormal morphologic features in most mast cells (Fig. 1, panels E–F). Flow cytometry confirmed the presence of a small population of mast cells (0.3% of events) with most demonstrating aberrant CD25 (Fig. 1, panel G) and CD2 expression. Molecular assessment of her marrow by quantitative polymerase chain reaction demonstrated a population harbouring an activating codon 816 mutation of KIT. Cutaneous mastocytosis in adults warrants careful evaluation to exclude systemic mastocytosis. Diagnostic criteria for systemic mastocytosis are categorized as major (multifocal dense aggregates of mast cells in extracutaneous organs) and minor (including abnormal mast cell morphology or antigen expression, elevated serum tryptase, and activating KIT mutations). Diagnosis requires the major criterion and at least one minor criterion to be met, or at least three minor criteria in the absence of the major criterion. Despite the absence of overtly increased mast cell numbers and complete absence of mast cell aggregates, the patient was diagnosed with systemic mastocytosis based on the presence of abundant morphologically atypical mast cells in her bone marrow, aberrant mast cell CD2 and CD25 expression, and an activating KIT mutation, emphasizing the potential morphologic subtlety of mastocytosis in tissue evaluation and the importance of targeted ancillary testing for accurate diagnosis of mast cell neoplasms.